Access
To read this story in full you will need to login or make a payment (see right).
Article
Nature Medicine 11, 175 - 182 (2005)
Published online: 30 January 2005 | doi:10.1038/nm1187
Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice
Tohru Uchida1,5, Takehiro Nakamura1,5, Naoko Hashimoto1, Tomokazu Matsuda1, Ko Kotani1, Hiroshi Sakaue1, Yoshiaki Kido1, Yoshitake Hayashi2, Keiichi I Nakayama3, Morris F White4 & Masato Kasuga1
Abstract
The protein p27Kip1 regulates cell cycle progression in mammals by inhibiting the activity of cyclin-dependent kinases (CDKs). Here we show that p27Kip1 progressively accumulates in the nucleus of pancreatic beta cells in mice that lack either insulin receptor substrate 2 (Irs2-/-) or the long form of the leptin receptor (Lepr-/- or db/db). Deletion of the gene encoding p27Kip1 (Cdkn1b) ameliorated hyperglycemia in these animal models of type 2 diabetes mellitus by increasing islet mass and maintaining compensatory hyperinsulinemia, effects that were attributable predominantly to stimulation of pancreatic beta-cell proliferation. Thus, p27Kip1 contributes to beta-cell failure during the development of type 2 diabetes in Irs2-/- and Lepr-/- mice and represents a potential new target for the treatment of this condition.
To read this story in full you will need to login or make a payment (see right).
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
Organ alchemy: producing insulin in the liverNature Medicine News and Views (01 May 2003)
Diabetes in midlife: Planting genetic time bombsNature Medicine News and Views (01 Oct 1997)
See all 3 matches for News And ViewsRESEARCH
A test of the role of the proximal histidines in the Perutz model for cooperativity in haemoglobinNature Structural Biology Article (01 Jan 1997)
Intravenous grafts recapitulate the neurorestoration afforded by intracerebrally delivered multipotent adult progenitor cells in neonatal hypoxic?ischemic ratsJournal of Cerebral Blood Flow & Metabolism Original Article
See all 64 matches for Research